Neuroendocrine tumors (NET) arise from the diffuse neuroendocrine system in the gastrointestinal tract, bronchopulmonary system, and the urogenital tract. Generically these tumors have been referred to as carcinoid tumors, but more recent scientific evaluation introduced by the World Health Organization has reclassified them as NET based on size, proliferative rate, localization, differentiation, and hormone production. Neuroendocrine tumors can be a low-grade malignancy (carcinoid tumor)1 or a more aggressive variant. This tumor rarely metastasizes to the ocular region. However, when this does occur, gastrointestinal NET typically spreads to the orbit, whereas bronchial NET classically metastasizes to the choroid.2

Ocular ultrasonography is important in differentiating carcinoid metastasis from amelanotic melanoma in that metastasis is usually echogenic while melanoma is typically echolucent.3,4 Occasionally, melanoma can also show intralesional cavitation, a feature not previously described with metastases. In this article, we describe a new observation of cavitation within biopsy-proven NET (carcinoid) metastasis in 3 cases.

REPORT OF CASES

Case 1

A 59-year-old, asymptomatic, healthy woman was found to have an amelanotic choroidal mass in her left eye on routine examination. Visual acuity measured 20/20 OU. The mass measured 4 × 4 × 2 mm. Ocular ultrasound showed medium acoustic hollowness and medium internal reflectivity. The lesion remained stable for 4 years but then showed growth to 16 × 15 × 8 mm. (Figure, A) Two new, smaller tumors were also noted. On ocular ultrasonography, the main lesion was acoustically solid, with a well-defined, acoustically hollow cavity occupying approximately 40% of the mass (Figure, B). The diagnosis was multiple choroidal metastases, the largest with cavitation. Systemic evaluation revealed biopsy-proven primary bronchial NET with clinical features of carcinoid syndrome. Plaque radiotherapy was performed. Thirteen months after therapy, the patient died of systemic complications of metastatic NET.

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Figure.

Neuroendocrine tumor (NET) metastasis to the choroid demonstrating cavitation. A and B, A 59-year-old woman with choroidal metastasis from lung NET was found to have a large amelanotic choroidal metastasis (A) with surrounding subretinal fluid. B-scan ultrasonography (B) showed a dome-shaped echodense choroidal mass of 7.8 mm thickness with central cavitation occupying approximately 40% of the mass. C and D, A 77-year-old woman with choroidal metastasis from lung NET was found to have a large amelanotic choroidal metastasis (C), shown on fine-needle aspiration biopsy. B-scan ultrasonography (D) showed an echogenic dome-shaped choroidal mass with central cavitation, occupying approximately 30% of the mass. E and F, A 77-year-old woman with bilateral multifocal metastasis from lung NET tumor demonstrated a large amelanotic choroidal metastasis (E) with cavitation on B-scan ultrasonography (F) occupying approximately 20% of the mass. G and H, Following enucleation, microscopic analysis of case 3 revealed a fluid-filled cavity within the tumor without surrounding inflammation or necrosis seen on low power (G; hematoxylin-eosin; original magnification ×15) and without a continuous endothelial lining on higher magnification (H; hematoxylin-eosin; original magnification ×250).

Case 2

A 77-year-old woman with breast cancer developed blurred vision in the right eye and was found to have an amelanotic choroidal mass, presumed to represent breast cancer metastasis. Her visual acuity was 20/50 OD and 20/20 OS. The mass measured 12 × 12 × 7 mm and showed associated subretinal fluid (Figure, C). B-scan ultrasonography revealed an echogenic mass with an acoustically hollow cavity occupying 30% of the mass (Figure, D). Fine-needle aspiration biopsy revealed an NET with morphology and immunocytochemical staining (positive AE1/AE3, EMA, chromogranin, synaptophysin and negative HMB45, Melan A, CD45) suggestive of carcinoid tumor. Systemic evaluation found a primary tumor in the lung and possible liver metastases. Plaque radiotherapy was performed, and the tumor regressed to 2.6 mm on the last follow-up visit 4 months later. The liver neuroendocrine metastases were later confirmed by biopsy and the patient started receiving chemotherapy.

Case 3

A 77-year old woman with a 4-year history of nonproductive cough had a 4-month history of progressive blurred vision in the left eye. Her visual acuity was 20/20 OD, and hand motions OS. Fundus examination showed 2 subtle, amelanotic, acoustically solid choroidal masses on the right eye located along the inferotemporal arcade measuring 3 × 1.5 × 1.5 mm and 1 × 1 × 0.5 mm with no associated subretinal fluid. In the left eye, there was a solitary amelanotic mass measuring 13 × 12 × 6.4 mm with serous retinal detachment. (Figure, E) On ultrasonography, the acoustically solid mass displayed a hollow central cavity occupying 20% of the mass. (Figure, F) Fine-needle biopsy disclosed pleomorphic cells more consistent with melanoma than metastasis. Therapeutic options included radiotherapy or enucleation, and the patient preferred enucleation of the left eye. Gross examination of the enucleated eye showed a tan choroidal mass with overlying shallow retinal detachment. Microscopic analysis of the lesion (previously described5) showed a malignant neoplasm with pigmented dendritiform cells with slender processes and a fluid-filled, intralesional cavity without an endothelial lining. There was no area of necrosis, hemorrhage, or inflammation surrounding the cystic cavity. There was no sign of trauma from the needle biopsy inducing the cavity. Immunohistochemical staining of the mass showed immunoreactivity for cytokeratin markers (CAM 5.2, AE1), calcitonin, chromogranin, and synaptophysin, features that were indicative of a metastatic NET. Results of immunoreactivity testing for melanoma marker HMB45, as well as S100, vimentin, and breast carcinoma markers were negative. Systemic evaluation revealed a lung nodule on the right middle lobe with positive immunoreactivity to AE1, calcitonin, chromogranin, and synaptophysin, consistent with NET.5 On the last follow-up visit at 22 months, her visual acuity remained unchanged in the right eye and the choroidal metastases were stable.

COMMENT

Cavitation of an intraocular tumor has been documented with uveal melanoma, ciliary body melanocytoma, and retinoblastoma.6- 12 Cavitary melanoma can show unifocal or multifocal cavities, some of which occupy up to 90% of the tumor.8 The origin of intratumoral cavities is speculated to be the result of tumor necrosis, intralesional hemorrhage or accumulation of mucoproteinaceous substance.7,8 With retinoblastoma, intratumoral cavities are suggestive of well-differentiated retinoblastoma that show minimal response to chemotherapy and radiotherapy.6

The differentiation of a choroidal metastasis from amelanotic melanoma depends on several clinical features as well as diagnostic testing with fluorescein angiography and ultrasonography.2- 4 It is well established that most metastatic tumors appear echodense on B-scan and show medium to high internal reflectivity on A-scan ultrasonography.2- 4 Melanoma tends to be echolucent on B-scan and show low internal reflectivity on A-scan ultrasonography.2- 4 Until now, cavitation within a choroidal lesion was most suggestive of a melanoma. In this study, we found cavitation within 3 choroidal metastases, all of which proved to be large NET from primary site in the lung. Based on this finding, patients who present with a cavitary amelanotic choroidal mass should have systemic evaluation for a primary cancer and possible confirmation with fine-needle aspiration biopsy of the intraocular tumor, as large choroidal metastases as well as melanoma can show cavitation.

Figures

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Figure.

Neuroendocrine tumor (NET) metastasis to the choroid demonstrating cavitation. A and B, A 59-year-old woman with choroidal metastasis from lung NET was found to have a large amelanotic choroidal metastasis (A) with surrounding subretinal fluid. B-scan ultrasonography (B) showed a dome-shaped echodense choroidal mass of 7.8 mm thickness with central cavitation occupying approximately 40% of the mass. C and D, A 77-year-old woman with choroidal metastasis from lung NET was found to have a large amelanotic choroidal metastasis (C), shown on fine-needle aspiration biopsy. B-scan ultrasonography (D) showed an echogenic dome-shaped choroidal mass with central cavitation, occupying approximately 30% of the mass. E and F, A 77-year-old woman with bilateral multifocal metastasis from lung NET tumor demonstrated a large amelanotic choroidal metastasis (E) with cavitation on B-scan ultrasonography (F) occupying approximately 20% of the mass. G and H, Following enucleation, microscopic analysis of case 3 revealed a fluid-filled cavity within the tumor without surrounding inflammation or necrosis seen on low power (G; hematoxylin-eosin; original magnification ×15) and without a continuous endothelial lining on higher magnification (H; hematoxylin-eosin; original magnification ×250).

Correspondence

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